Honeycomb lung refers to the characteristic appearance of variably sized cysts in a background of densely scarred lung tissue. Microscopically, enlarged airspaces surrounded by fibrosis with hyperplastic or bronchiolar type epithelium are present. [1] However, these changes are nonspecific and are often seen in numerous end-stage interstitial lung diseases (ILDs). [2] Recognition of honeycomb change is imperative as its presence is associated with a poor prognosis.
- The honeycomb change is the
- end result of
- chronic interstitial inflammation and fibrosis.
- destruction of normal lung architecture
- Resulting in
- cystic airspaces
- the result of progressive destruction of normal lung tissue and the replacement of the destroyed tissue by fibrosis. lined by
- thickened fibrous tissue and
- surrounded by areas of dense fibrosis
- cystic airspaces
The exact mechanism underlying the honeycomb change in UIP is not fully understood, but it is believed to be the result of a combination of factors, including:
- Persistent lung injury: Chronic injury to the lung tissue leads to the accumulation of scar tissue and destruction of normal lung architecture.
- Abnormal wound healing: Abnormal wound healing response to the chronic lung injury leads to the formation of dense fibrosis.
- Altered surfactant metabolism: Altered metabolism of surfactant, which is a substance that helps to keep the air sacs in the lungs open, can lead to collapse of the air sacs and the formation of cystic airspaces.
- Impaired regeneration: Impaired regeneration of lung tissue due to aging or other factors may also contribute to the development of honeycomb change in UIP.
In summary, the honeycomb change in UIP is the result of chronic interstitial inflammation and fibrosis, which leads to the destruction of normal lung tissue and the formation of cystic airspaces surrounded by areas of dense fibrosis.
Honeycomb lung is subpleural in location because the subpleural area is more susceptible to injury and fibrosis than other areas of the lung.
The subpleural area is the region just beneath the pleura, which is a thin membrane that lines the surface of the lungs and the inside of the chest wall. The subpleural area is the site where the alveoli (air sacs) are located and is involved in gas exchange between the lungs and the bloodstream.
In usual interstitial pneumonia (UIP), which is the most common cause of honeycomb lung, there is chronic inflammation and fibrosis of the lung tissue. The subpleural area is more exposed to environmental insults, such as inhaled irritants, viral infections, or autoimmune processes, that can lead to chronic inflammation and injury of the lung tissue. The subpleural area is also more susceptible to mechanical stress, such as the strain that occurs during breathing, which can contribute to the development of fibrosis.
Furthermore, the subpleural area is relatively poorly vascularized and has less supportive tissue than other areas of the lung, making it more prone to injury
Ashley Davidoff TheCommonVein.net
lungs-0738b
In patients with interstitial lung disease, the inflammatory process and interstitial fibrotic disease progresses and the walls between the alveoli are destroyed causing large subpleural, variably sized, subpleural, thick walled, stacked, cystic spaces . The appearance is reminiscent of a honeycomb and indicates end stage fibrosis
Ashley Davidoff MD thecommonvein.net lungs-0738bh
subpleural regions of the lung and are most severe in the lower lobes and lower portions of all lobes (see the image below).
Ashley Davidoff MD TheCommonVein.net
Source Public Domain
Honeycomb changes in ILD is a feature on CT of interstitial lung disease and is characterised by clusters of stacked cystic air spaces in the periphery and predominantly posteriorly at the bases of the lungs . They likely represent small airways that have been denuded of the their alveoli apparatus. It is most commonly associated with idiopathic pulmonary fibrosis (IPF) and its radiological equivalent UIP – usual interstitial pneumonia.
81f lungs uip 004
Ashley Davidoff
TheCommonVein.net
Ashley Davidoff
TheCommonVein.net
Ashley Davidoff MD TheCommonVein.net honeycomb changes 77-001
Honeycombing results from the deposition of dense collagen fibers that destroy the characteristic alveolar structure,5 and is typically representative of end-stage lung disease.7 On HRCT, honeycomb cysts appear as enlarged airspaces that are often irregular in size, share thick walls, and are stacked upon one another. The cysts are typically 3-10 mm in diameter but can be as large as 2.5 cm.57 When associated with a pattern of usual interstitial pneumonia typical of idiopathic pulmonary fibrosis, honeycombing typically has a peripheral, basal, and subpleural distribution.45 The percentage of patients with IPF with honeycombing on HRCT varies in the literature, but it is estimated to be observed in one-third to two-thirds of patients.89
Radiology Rounds
Distinguishing between honeycombing and paraseptal emphysema may be difficult, especially when coexisting on a single scan. As compared with honeycombing, which may present as multiple layers of cysts stacked upon one another, emphysema presents as a single layer of holes without stacking.7 Furthermore, emphysematous holes are typically not hexagonal; therefore, the shape of the cysts and their propensity to stack can help to distinguish one from the other.7
Histologic specimen shows dilated air spaces lined by bronchiolar type epithelium and surrounding fibrosis consistent with microscopic honeycomb change. Courtesy Medscape
Typical histological finding of spatial heterogeneity in usual interstitial pneumonia (UIP) with an abrupt transition from honeycomb change (left) to normal lung (right) using trichrome stain, X40)
Courtesy Medscape eMedicine
Axial CT through the base of the lungs shows honeycombing change sin the posterior segment of the left lower lobe characterized by the stacking of cystic spaces.
Ashley Davidoff MD
Coronal reconstruction CT through the posterior portion of the lungs shows honeycombing change sin the posterior segment of the left lower lobe characterized by the stacking of cystic spaces.
Ashley Davidoff MD
Sagital reconstruction CT through the posterior portion of the lungs shows honeycombing change sin the posterior segment of the left lower lobe characterized by the stacking of cystic spaces.
Ashley Davidoff MD
“In UIP, the fibrotic process produces
patchy but diffuse changes in end-stage lung disease. Endstage lung disease, as defined morphologically, represents the
culmination of a ‘‘dying-back’’ process of acini within the
secondary pulmonary lobule. One may conceptualize this
with respect to lung embryogenesis. The lung in utero
develops from the foregut and undergoes pseudoglandular,
canalicular, and alveolated stages, which roughly correspond with the trimesters of pregnancy, respectively. The
mature lung is capable of gas-exchange because of
alveolation. Usual interstitial pneumonitis, in an admittedly
crude manner, reverses this sequence, so that the alveolated
lung is deconstructed to a set of ‘‘glandular’’ airways
surrounded by fibrosis.
Lung: Time for a Change—Kradin
What is the ‘‘end-stage’’ of the acinus? When the
alveolated structures are lost, a distorted ectatic terminal
bronchiole, lined by bronchiolar epithelium, is left, which is
why the changes of UIP are dominantly subpleural or
periseptal, because this is where distal lung acini terminate.
Accordingly, end-stage lung disease should show no
intervening healthy alveolated structures between the
ectatic bronchiole and the subjacent visceral pleura or septa.
The HRCT appearance of end-stage lung should include
microcysts associated with scar and no evident distal
alveolated lung parenchyma.
Currently, the early radiographic diagnosis of UIP is
hampered by 2 factors: the requirement for identifying
honeycomb lung, the other, confusion with traction bronchiolectasis. Honeycomb lung is reminiscent of the appearance
of the honeycomb of a beehive. This reflects the stacking of
ectatic bronchioles in which no alveolated lung intervenes. It
is not, however, a biological term and, therefore, lacks the
sensitivity of the pathologist’s microscopic examination
where foci of end-stage lung disease can be identified with
confidence before the stacking of ectatic bronchioles has
developed. In my experience, cystic bronchiolectasis can be
seen in computed tomography scans without honeycombing,
and many of these cases will prove to have UIP on biopsy. A
careful examination of the subpleural lung should show no
intervening zone of aerated lung between the microcysts and
the visceral pleura. The recent introduction of dual-energy
HRCT scanning may increase the sensitivity for detecting
alveolated structures, allowing for an earlier, noninvasive
diagnosis of UIP”
I recommend that the phrase intralobular fibrous obliteration with microcysts be adopted by both radiologists and
pathologists to reflect the bronchiolectasis and peripheral
scarring of the end-stage lung in UIP. Even a few subpleural
microcysts in the periphery of a diffusely fibrotic lung may represent early UIP. The current binary reading, based on
the presence or absence of honeycomb lung, potentially
renders a disservice to clinicians who must make critical
diagnostic and therapeutic decisions. To avoid reducing the
specificity of computed tomography scanning in the
diagnosis of UIP, the phrase intralobular fibrous obliteration
with microcysts may require modifiers. Three examples of
suggested HRCT diagnoses are given below:
1. ‘‘Diffuse patchy interstitial fibrosis with subpleural
intralobular fibrous obliteration showing multiple microcysts. This appearance is diagnostic for UIP.’’
2. ‘‘Diffuse interstitial fibrosis with occasional subpleural
intralobular cystic spaces. This appearance favors early
UIP, but biopsy confirmation may be indicated.’’
3. ‘‘Diffuse interstitial fibrosis with cystic airways with a zone
of alveolated lung identified subjacent to the visceral
pleura. The findings are most consistent with nonspecific
interstitial pneumonitis and traction bronchiectasis. Clinical and pathologic correlation may be required.’’
The phrase intralobular fibrous obliteration with cystic
changes is accurate; honeycomb lung, although commonplace
and widely adopted, is difficult to define and meaningless
biologically. It is also insensitive to early or milder disease.
In addition, the term honeycomb lung is not necessarily
helpful for pathologists who may think they know what it is. In
classic cases of UIP, the cystic bronchioles should be lined by
respiratory ciliated epithelium, but in a subset of cases, the
cysts of diffusely fibrotic lungs are instead lined by cuboidal
epithelium. These examples of honeycomb lung show distinct
epithelial expression of FoxF1 and SSH proteins, gene
products that have a role in lung development.7 I suggest that
pathologists pay attention not only to whether there is patchy
diffuse scarring and microcystic, honeycomb’’ changes in
diagnosing UIP but also to the nature of the epithelium lining
the microcysts because this may reflect distinct pathways of
structural simplification and lung remodeling with pathogenetic and clinical significance. In my own practice of
pulmonary pathology, I limit a definitive diagnosis of UIP to
cases where cystic bronchiolectasis with respiratory epithelium
is identified. Attempting to cubbyhole diagnoses likely will not
advance our knowledge of these diseases. Therefore, adhering
to strict criteria for what represents the diagnosis of UIP may
prove to be an important advance for both the diagnosis and
the ultimate understanding and treatment of this disorder”
Reprints: Richard L. Kradin, MD, Department of Pathology,
Massachusetts General Hospital, 55 Fruit St, Warren 253, Boston,
MA 02114-2696 (e-mail: rkradin@partners.org).
1398 Arch Pathol Lab Med—Vol 139, November 2015 Honeycomb